PubMed Health⌕ Search

Biomedical subjects

P C Wynn

Publications and source records attributed to P C Wynn.

At least 19 recordsLinked to original sources
PubMed2006

Lactational performance of Quackenbush Swiss line 5 mice.

We evaluated 2 strains of mice for their utility in the investigation of nutritional and molecular regulatory mechanisms of lactation. The lactational performance and milk composition were characterized for an inbred mouse strain, inbred Quackenbush Swiss line 5 (QSi5) selected persistently for fecundity, and a nonselected strain, CBA. The milk yield assessed by changes in BW in response to suckling of sustainable litter sizes for each strain was 3-fold greater (P < 0.001) in QSi5 mice than the CBA strain. The QSi5 mice also produced milk more efficiently (P < 0.001) than CBA mice, despite having the same quantity of mammary tissue per unit of BW. Milk composition did not vary between strains or by stage of lactation, with the exception of lactose concentration, which was greater (P = 0.003) in QSi5 mice. Expression of epsilon-casein was > or = 10-fold greater, and alpha(S1)-casein was > or = 3-fold greater, during mid and late lactation compared with early lactation in both strains, whereas kappa-casein underwent an apparent alteration in posttranslational modifications in both strains from early to mid lactation. Changes in casein composition coincided with an increased susceptibility to proteolytic degradation; hence milk from early lactation may be more readily degraded to facilitate digestion in the neonate. The greater milk synthetic capacity of QSi5 mice over the lactation cycle provides a useful model for studies of nutritional and molecular regulation of lactation.

Animals↗
PubMed2005

The effect of active immunization against adrenocorticotropic hormone on cortisol, beta-endorphin, vocalization, and growth in pigs.

Because the poor growth performance of intensively housed pigs is associated with increased circulating glucocorticoid concentrations, we investigated the effects of glucocorticoid suppression by inducing a humoral immune response to ACTH on physiological and production variables in growing pigs. Grower pigs (28.6 +/- 0.9 kg) were immunized with amino acids 1 through 24 of ACTH conjugated to ovalbumin and suspended in diethylaminoethyl (DEAE) dextran-adjuvant or adjuvant alone (control) on d 1, 28, and 56. The ACTH-specific antibody titers generated suppressed increases in cortisol concentrations on d 63 in response to an acute stressor (P = 0.002; control = 71 +/- 8.2 ng/mL; ACTH-immune = 43 +/- 4.9 ng/mL) without altering basal concentrations. Plasma beta-endorphin concentrations were also increased (P < 0.001) on d 63 (control = 18 +/- 2.1 ng/mL; ACTH-immune = 63 +/- 7.3 ng/mL), presumably because of a release from negative feedback on the expression of proopiomelanocortin in pituitary corticotropes. Immunization against ACTH did not alter ADG (P = 0.120; control = 1,077 +/- 25; ACTH-immune = 1,143 +/- 25 g) or ADFI (P = 0.64; control = 2,719 +/- 42; ACTH-immune = 2,749 +/- 42 g) and did not modify behavior (P = 0.681) assessed by measuring vocalization in response to acute restraint. In summary, suppression of stress-induced cortisol responses through ACTH immunization increased beta-endorphin concentrations, but it did not modify ADG, ADFI, or restraint vocalization score in growing pigs.

Adrenocorticotropic Hormone↗
PubMed2000

Effects of genetic merit and varying dietary protein degradability on lactating dairy cows.

Eighty two multiparous Holstein cows were blocked by genetic merit (high vs. low) and assigned to one of two treatments [high rumen-undegradable protein (RUP): rumen-degradable protein (RDP) vs. low RUP: RDP] from d 21 before to d 150 after calving to study the effects of these treatments on production and reproductive performance. Diets were isonitrogenous (dry cow 10.5% crude protein; lactating cow 19.3%), isoenergetic (dry cow 10.0 MJ of metabolizable energy (ME); lactating cow 10.9 MJ of ME) and fed as total mixed rations. Feeding more RUP significantly increased dry matter intake and milk yield, reduced body tissue mobilization, and lowered concentrations of serum nonesterified fatty acids (NEFA) and plasma urea. Expression of estrus at first ovulation was improved, first service conception rate was higher, and calving to conception interval was shorter for the high RUP group. Cows of high genetic merit produced more milk, mobilized more body tissue, and had higher concentrations of plasma growth hormone. The dry matter intake and concentrations of blood metabolites did not significantly differ with genetic merit. Expression of estrus at first ovulation was significantly lower for cows of high genetic merit. Serum NEFA concentrations were significantly higher, and estrus was not observed at first ovulation for cows of higher genetic merit fed the low RUP diet. The interaction between dietary RUP and genetic merit was not significant for other measures of performance or fertility. Feeding a low RUP: high RDP diet had negative effects on some aspects of production and reproductive performance. The effects of diet on NEFA concentrations and estrus display were greater in cows of high genetic merit, indicating that potential interactions should be evaluated in future reproductive studies involving protein and fertility.

Adipose Tissue↗
PubMed1998

The effects of fibroblast growth factors 1 and 2 on fibre growth of wool follicles in culture.

The effects of fibroblast growth factor-1 (FGF-1) and FGF-2 on fibre growth and follicle function were examined using a previously described procedure to culture wool follicles. Because the FGFs bind to glycosaminoglycan components of the extra-cellular matrix, we also investigated interactions between FGF-1 and FGF-2 with heparin on wool fibre growth. Individual follicles were microdissected from Merino sheepskin and transferred to culture. Follicles increased in length for 6 days, and in all groups, no significant differences in follicle length were observed. Increase in follicle length was associated with fibre growth, follicles maintained normal anagen morphology and incorporated [3H]thymidine into the bulb and outer root sheath cells. Follicles in all treatments continued to produce fibre keratins, as detected by immunohistochemistry. However, the patterns of fibre and cytoskeletal proteins incorporating [35S]methionine in control and treated follicles were significantly different. We found a considerable decrease in the intermediate filament keratins or low sulphur proteins in follicles cultured in the presence of FGF-1 and FGF-2 compared to controls. The majority of proteins detected in these samples were acidic high sulphur proteins. These studies provide evidence for a specific role for the fibroblast growth factors in the regulation of fibre differentiation.

Animals↗
PubMed1996

Effects of epidermal growth factor and transforming growth factor alpha on the function of wool follicles in culture.

The development of a procedure to culture wool follicles from Merino sheep in serum-free conditions has enabled us to investigate the actions of epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha) on follicle function, including fibre growth. Follicles grown in the absence of growth factors maintained their anagen morphology for 6 days as determined by light microscopy. During this time they incorporated [3H]thymidine into the DNA of the bulb matrix and outer root sheath (ORS) cells and produced fibre keratins as detected by immunohistochemistry. In the presence of EGF and TGF alpha, fibre production ceased after 4 days, as it does following the administration of EGF in vivo. Cessation of fibre growth was not accompanied by regression of the follicle bulb which occurs in vivo. Follicle length growth did not differ significantly from controls and cells in the bulb continued to proliferate. Usually, the structure of the dermal papillae resembled that in control follicles, which was also in marked contrast to changes reported in vivo. In EGF- and TGF alpha-treated follicles, [3H]thymidine continued to be incorporated into DNA of the ORS and bulb after fibre growth ceased. Although wool keratin synthesis ceased, cytokeratins of the epidermis and ORS continued to be produced in the bulb as detected by immunochemistry. These bulb cells were also positive for the periodic acid-Schiff (PAS) reaction indicating the presence of glycogen, a normal component of ORS cells. The observations that cell proliferation continued in the bulb, that glycogen was present and that soft keratins were expressed in these cells suggest that the bulb cell population was induced to differentiate into an ORS phenotype by EGF and TGF alpha.

Animals↗
PubMed1995

Characterization and distribution of epidermal growth factor receptors in the skin and wool follicles of the sheep fetus during development.

We have determined the binding affinity and capacity and relative distribution of epidermal growth factor (EGF) receptors in the skin of the Merino sheep fetus before and during the development of the wool follicle population. Autoradiography of tissue sections incubated with [125I]EGF revealed that label was confined predominantly to the epidermis and dermoepidermal junction before follicle formation, at 30 and 55 d of gestation. During follicle initiation (Days 60 to 65), receptor activity was distributed over the epidermis, including the epidermal aggregations of primordia at the dermoepidermal junction. However, receptor concentrations, as revealed by grain counts of autoradiographs, were reduced in these regions when compared with 55-d skin. The receptor distribution over the epidermis and its derivatives did not alter during subsequent follicle development, although the intensity of labeling increased as the follicles matured. Specific receptor binding was not observed above background levels in the dermis and dermal papillae during all stages of follicle development. At follicle maturation, EGF receptors were widely distributed over the cells of the epidermis and the epidermal derivatives of the cutaneous appendages but were particularly localized in the sebaceous glands and outer root sheath (see also Wynn et al. 1989). EGF immunoreactive material has also been found at these sites (du Cros et al. 1992), suggesting an autocrine role for EGF in the regulation of cell function. It is likely that the differentiation-promoting activities of EGF may predominate over those of growth, because the receptor-bearing cells were not members of rapidly proliferating populations.

Animals↗
PubMed1994

Growth of wool follicles in culture.

A procedure for the culture of isolated wool follicles from Merino sheep is described. Follicles were microdissected from midside skin samples of 2-yr-old wethers and transferred, individually, to 24-well tissue culture plates. When maintained in supplemented Williams' E medium containing 5 to 10% fetal bovine serum (FBS), insulin, hydrocortisone, and a trace element mixture, fibre growth rates of 40 to 80 microns/day were observed. Follicles maintained their morphologic integrity for up to 7 days, incorporated [methyl-3H]thymidine into DNA and [35S]methionine into intermediate-filament keratins of the growing fiber. Insulin and hydrocortisone stimulated fiber growth at concentrations of 10 micrograms/ml and 50 ng/ml, respectively, but higher doses were inhibitory. The growth of fibers in response to hydrocortisone and the changes in follicle morphology was similar to those induced in skin after systemic administration of cortisol in vivo. A positive interaction between hydrocortisone and trace elements for follicle survival and hydrocortisone, insulin, and FBS for fiber growth was also found. The successful culture of Merino sheep follicles provides a model with which to study the direct influence of endocrine, nutritional and local factors on wool keratin synthesis independently of systemic shifts in the animals' metabolism.

Aging↗
PubMed1992

The development of corticosteroid binding globulin-like activity in fetal sheep blood.

Parturition in sheep is initiated by the fetus and is preceded by a rise in fetal cortisol and corticosteroid-binding globulin (CBG) late in gestation. In this study plasma cortisol and CBG concentrations were measured in fetal and maternal circulation from 40 days gestation to early post-partum. The fetal cortisol profile was shown to be triphasic in nature; being high in both the first and last trimester but low in the middle period of gestation. In the last trimester, total cortisol increased steadily, reaching it's highest level just prior to parturition (145 days gestation), before falling to maternal levels over the first 10 days post-partum. The changes seen in CBG concentrations throughout gestation and post-partum mirrored the triphasic nature seen in cortisol levels. CBG was significantly higher at 40, 56 and 140 days gestation than at mid-gestation (77 and 90 days). However, at 145 days gestation there was a significant fall in CBG levels. CBG levels were higher at 1 day post-partum when compared to 145 days gestation, the former rapidly falling to maternal levels over the subsequent 9 days. The maximum binding capacity at 40, 56, 70 and 90 days gestation exceeds the total serum cortisol concentration. However at 140 and 145 days gestation and 1 day post-partum the total serum cortisol exceeds the Bmax. The highest cortisol:Bmax ratio is seen at 145 days gestation due to the fall of CBG binding capacity at this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

Hair growth induction: roles of growth factors.

The hair follicles of eutheria arise during fetal life as a consequence of interactions between the cells and matrices of the epidermis and mesenchyme. In some instances, communication may be mediated by growth factors, receptors, and similar molecules. We have focused on epidermal growth factor and fibroblast growth factor, since both are expressed in skin, where they are presumed to perform regulatory functions. In sheep, EGF receptors are located on skin epithelia. An EGF-like protein was detected by immunochemistry in fetal epidermis but was not associated with the cells of developing wool follicles. During subsequent development the molecule was associated with the sebaceous glands and the outer root sheath. If the ORS may be considered a source of stem cells for the proliferating matrix, EGF may act as a differentiation factor, determining cell fates by cell contact mechanisms similar to those in invertebrates. FGF was localized in the epidermis and basal lamina and in follicle plugs during morphogenesis. At maturity, FGF was found in the ORS and in the region of the basal lamina of the follicle bulb, suggesting a role in bulb proliferation and fiber growth.

Aging↗
PubMed1991

Influence of nutritional status on growth hormone-dependent circulating somatomedin-C activity in mature sheep.

The effect of daily administration of ovine GH for a period of 4 weeks on somatomedin-C biological activity in plasma was investigated in mature Merino sheep fed a maintenance energy intake (low plane; LP) or 1.6 times this amount (high plane; HP). The GH treatment resulted in a significant (P less than 0.05) increase in plasma GH levels in blood samples collected 23.5 h after each daily injection in both LP and HP groups. Plasma concentrations of somatomedin-C activity and insulin were significantly stimulated to a maximum level by the third GH injection and remained at this level for 7 days. Subsequently, circulating levels of both hormones fell to 40-50% of the peak response to GH and returned to basal levels within 48 h of the cessation of GH injections. In the HP group the response of plasma insulin and somatomedin-C activity to GH injection was greater than in the LP group.

Animals↗
PubMed1989

Characterization and localization of receptors for epidermal growth factor in ovine skin.

Specific receptor sites for murine epidermal growth factor (EGF) have been characterized and their distribution determined in ovine skin. Binding of 125I-labelled EGF to skin membrane particles was temperature- and time-dependent, with equilibrium being reached within 1 h at 23 degrees C. Analysis of skin biopsies collected from ten castrated Merino sheep demonstrated the presence of a single class of saturable, high-affinity binding sites with a dissociation constant of 64 +/- 4 (S.E.M.) pmol/l and a binding capacity of 33.8 +/- 4.5 fmol/mg protein. Skin particle binding of 125I-labelled EGF was inhibited equipotently by mouse salivary gland EGF, EGF produced by recombinant DNA procedures and urogastrone. The EGF peptides 1-48, 6-53 and 7-53, derived from the native molecule by enzymatic cleavage, were much less potent. The relative binding potency of these molecules was correlated with their ability to induce precocious eyelid opening in mice and to inhibit wool follicle activity. Synthetic fragments representing the major structural domains of the EGF molecule (EGF(29-44), EGF(33-42) and EGF(3-31] were inactive in both the receptor and bioassays. Autoradiography of skin sections incubated with 125I-labelled EGF in vitro or of sections from skin which was perfused with 125I-labelled EGF in vivo demonstrated that EGF receptors were localized in undifferentiated cells of the epidermis and sebaceous glands, the inner and outer root sheath and bulb of wool follicles and in dermal arterioles. Differences in receptor concentration were observed between follicles following in-vivo perfusion of 125I-labelled EGF but not when the in-vitro labelling technique was used. The presence of receptors in these regions is consistent with the morphological changes in sheep skin in response to EGF administration which have been reported previously.

Animals↗
PubMed1988

Effects of growth hormone administration on wool growth in merino sheep.

The effects of daily administration of 10 mg of highly purified ovine growth hormone (GH) for a period of 4 weeks on wool growth have been measured in 12 Merino ewes fed either a calculated maintenance energy intake or 1.6 times this amount (six on each ration). Concentrations of hormones, glucose, urea, alpha-amino N and amino acids in the blood were monitored and faeces and urine collected for measurement of nitrogen balance. Wool growth rate decreased by 20% during the 4 weeks of GH treatment in sheep fed the high energy diet, largely because of reduced wool fibre diameter. This was followed by restoration of normal growth and then an increase of up to 20% above control levels, a response which persisted for 12 weeks following cessation of GH administration, and which was due to increases in both fibre length and diameter. GH administration caused marked increases in plasma concentrations of GH, insulin and somatomedin C, glucose and free fatty acids, all of which returned to basal levels following cessation of GH administration. No consistent changes in plasma concentration of T3, T4, cortisol, prolactin or alpha amino N were detected. Plasma urea and methionine levels decreased during GH treatment and returned to, or were raised above, basal levels after the GH treatment period. GH injection also resulted in a net retention of N during treatment, followed by a transient period of net N loss. The GH-induced changes in wool growth may be caused by a change in the partitioning of amino acids between the muscle mass and the skin. No other contributing factor(s) were identified.

Animals↗
PubMed1988

Corticotropin-releasing factor (CRF) induces desensitization of the rat pituitary CRF receptor-adenylate cyclase complex.

The rise in circulating ACTH levels after adrenalectomy in the rat is associated with a decrease in CRF receptor-binding capacity in the anterior pituitary. To investigate the role of increased hypothalamic CRF release on pituitary CRF receptor regulation after withdrawal of glucocorticoid feedback by adrenalectomy, the effects of chronic CRF infusion and lesions in the medial basal hypothalamus were studied in the rat. Subcutaneous infusion of CRF at 10, 25, 50, and 100 ng/min for 48 h in intact rats caused dose-dependent increases in plasma ACTH levels from the control value of 32.1 +/- 4.3 to 58.0 +/- 4.9, 82.0 +/- 7.1, 135.5 +/- 11.6, and 149.2 +/- 13.2 pg/ml, respectively. In contrast, the pituitary CRF receptor concentration was reduced by 25.3 +/- 4.5%, 38.3 +/- 2.5%, 43.8 +/- 0.9%, and 45.8 +/- 2.0%, respectively. Intravenous infusion of increasing doses of CRF caused a similar increase in plasma ACTH levels, which became maximum at the lowest infusion dose (32.4 +/- 5.4, 138.5 +/- 12.3, 162.0 +/- 18.3, and 167 +/- 19.1 pg/ml for control and 10, 50, and 100 ng/min CRF, respectively). Pituitary CRF receptor concentration was again decreased after iv CRF infusion [by 42 +/- 6.2% with the lowest dose (10 ng/min)], with no further reduction after infusion of 50 and 100 ng/min (49.0 +/- 6.8% and 26.0 +/- 6.2%, respectively)]. The decrease in pituitary CRF receptors after CRF infusion was accompanied by a decrease in CRF-stimulated adenylate cyclase activity, with a 10- to 100-fold increase in the concentration of CRF required for threshold stimulation. In cultured pituitary cells prepared from animals infused with 50 ng/min CRF for 48 h, maximum CRF-stimulated ACTH release was reduced by 29 +/- 3.2% (P less than 0.01; n = 3), with no significant change in sensitivity to CRF (ED50, 0.6 +/- 0.5 and 1.0 +/- 0.5 nM CRF for control and CRF infusion, respectively). The role of endogenous CRF in adrenalectomy-induced pituitary CRF receptor down-regulation was also studied in rats with medial basal hypothalamic deafferentation. The marked loss of pituitary CRF receptors after adrenalectomy was completely prevented by such hypothalamic lesioning, indicating that receptor down-regulation was dependent on the release of CRF or/and other hypothalamic factors. The data demonstrate that while increased CRF levels result in down-regulation and desensitization of pituitary CRF receptors, the differences between adrenalectomy and CRF infusion indicate that additional regulatory factors are involved in the modulation of CRF receptor content and activity after adrenalectomy.

Adenylyl Cyclases↗
PubMed1987

Receptors and actions of corticotropin-releasing hormone in the primate pituitary gland.

Receptors for CRH were identified in the pituitary gland of several primate species, and their binding characteristics were compared to the ability of CRH to elicit ACTH and cAMP responses in vitro. Autoradiographic analysis of the binding of [125I]Tyr-ovine CRH to frozen pituitary sections revealed CRH receptors in the intermediate and anterior lobes of human, marmoset, and cynomolgus monkey pituitaries. In the cynomolgus monkey, a high density of CRH receptors was present throughout the anterior and intermediate lobes. In the human pituitary, binding was concentrated in the anteromedial portion of the gland, whereas in the marmoset, binding was dense in the intermediate lobe and scattered as clusters throughout the anterior lobe. In membrane-rich fractions from the cynomolgus pituitary binding of [125I]Tyr-ovine CRH was time and temperature dependent, and was specific for CRH-related peptides; specific binding was increased by divalent cations and inhibited by guanyl nucleotides. Scatchard analyses of the binding data revealed a single class of high affinity sites [Kd, 1.93 +/- 0.23 (+/- SEM) nM], with a receptor concentration of 605 +/- 121 fmol/mg. In marmoset pituitary membranes, there were fewer receptors (200 +/- 15 fmol/mg), in agreement with the lower autoradiographic density of CRH binding. In anterior pituitary cell cultures from cynomolgus monkeys, CRH caused a dose-dependent stimulation of cAMP production and ACTH release, with half-maximum effective concentrations in the range of the CRH receptor affinity. Vasopressin and norepinephrine stimulated ACTH release to a much lesser extent, but both potentiated the stimulatory effect of CRH. Angiotensin II had no effect alone, but it also potentiated the effect of CRH. These data demonstrate the presence of CRH receptors in the primate pituitary, with characteristics similar to those in other species in their binding properties, coupling to adenylate cyclase, and functional interactions with other regulators of ACTH secretion that mediate the stimulatory effect of the peptide in the corticotroph.

Adrenocorticotropic Hormone↗
PubMed1987

Brain receptors for hypothalamic hormones.

Angiotensin II and CRF are but two of the several regulatory peptides which exert specific actions in the brain that are complementary with their peripheral effects upon end organs such as the anterior pituitary and adrenal glands. In the pituitary, the two peptides act in a coordinate manner on the corticotroph to regulate ACTH release. In the adrenal gland, angiotensin II receptors are abundant in the zona glomerulosa but are also present in the medulla, where the occurrence of CRF receptors and actions on catecholamine release reveals an additional site at which the two peptides exert related actions, in this case in the peripheral neuroendocrine system. Within the brain, the mapping of AII and CRF binding sites by topical autoradiography has provided new information about the distribution and potential functions of receptors for the two peptides. The central receptors for AII are distributed in a characteristic pattern in brain regions concerned with drinking, regulation of adrenergic function and arterial blood pressure, and control of pituitary hormone secretion. Thus, in addition to its recognized modulatory effects in the peripheral adrenergic system, angiotensin II may be involved in the central control of catecholamine release and action. A central action of AII on the release of regulatory peptides such as vasopressin and CRF, both of which are present in neurones of the paraventricular nucleus, is indicated by the high concentration of AII receptors in this region. Also, the high density of AII receptors in the median eminence suggests that AII modulates the hypothalamic secretion of neuropeptides such as CRF by actions at their site of release, as well as on the cell bodies of neurones responsible for peptide synthesis. The highly localized pattern of AII receptors at numerous specific sites in the brain differs from the more general distribution of many other CNS receptors, and reflects the selective actions of AII on discrete neural systems that subserve precisely integrated functions within the central nervous system. The widespread distribution of CRF receptors, with prominent localization in the cortical and limbic regions, is consistent with the more general neuroregulatory actions of CRF in the brain, and with the presence of immunoreactive CRF in several regions of the brain including the cortex, limbic system, and centers involved in the control of autonomic function. The cortical and limbic receptors are clearly relevant to the effects of centrally administered CRF on both behavioral and visceral responses, with prominent autonomic changes including increased catecholamine release and hypertension.

Angiotensin II↗